Evidence Supports the Use of Aspirin for Precision Chemoprevention of Colorectal Cancer

Cape Town, South Africa—Overwhelming evidence supports a chemopreventive benefit of aspirin on colo­rectal cancer (CRC), and a potential effect on other cancers and cardiovascular risk, according to Andrew T. Chan, MD, MPH, Chief, Clinical and Translational Epidemiology Unit, and Director, Gastroenterology Training Program, Massachusetts General Hospital, Boston, at the American Association for Cancer Research International Conference on New Frontiers in Cancer Research.

“Aspirin is potentially the chemopreventive agent for which there is the strongest evidence of effectiveness at prevention,” he said.

Consistent experimental and epidemiologic evidence has demonstrated an association between aspirin and a lower risk for CRC. In addition, 5 placebo-controlled, randomized controlled trials (RCTs) among patients with a history of colorectal adenoma or cancer showed that aspirin reduced the risk for recurrent adenomas, which are precursors to the vast majority of cancers, reported Dr Chan.

Aspirin’s Impact

Other modalities of CRC prevention rely heavily on screening—in particular, colonoscopy screening. Although there is widespread consensus that this type of screening is effective, certain limitations exist.

“It appears to be more successful in reducing the risk of distal colorectal cancer, and less successful in reducing the risk of proximal colon cancer. So there’s reason to consider other types of modalities, particularly modalities that are more cost-efficient,” Dr Chan said.

The CAPP2 RCT examined aspirin use among patients with the Lynch hereditary CRC syndrome, and data from long-term follow-up demonstrated that randomized aspirin treatment was associated with a lower-risk for CRC. The same results were demonstrated in the Women’s Health Study, an RCT that examined the effectiveness of aspirin for the primary prevention of cancer and cardiovascular disease.

“It’s very well-known that aspirin potentially has benefits for the prevention of cardiovascular disease,” Dr Chan noted. Secondary analyses of RCTs of aspirin for the prevention of cardiovascular disease have demonstrated reductions in the incidence of, and mortality from, CRC with regular aspirin use. In 8 cardiovascular RCTs, aspirin reduced the risk for overall cancer death.

“Cancer is poised to overtake cardiovascular disease as the leading cause of death in the US [United States], so aspirin can potentially have an impact on the 2 leading causes of mortality in much of the world,” he said.

In 2016, the US Preventive Services Task Force (USPSTF) updated its primary prevention guidelines for aspirin because of overwhelming evidence in support of its benefits. The USPSTF now recommends low-dose aspirin (81 mg daily) for the primary prevention for cardiovascular disease and CRC in adults aged 50 to 59 years, and possibly aged 60 to 69 years, with a >10% 10-year risk for cardiovascular events.

“This recommendation represents a significant milestone for the field of preventive medicine. With the exception of tamoxifen for women at high risk for breast cancer, this is the first medication broadly recommended for cancer prevention by the USPSTF,” said Dr Chan.

Personalizing Chemoprevention

Despite increased recognition of the effectiveness of aspirin as chemoprevention, wider-scale efforts are limited because of concerns over its established association with gastrointestinal bleeding. The hazards associated with long-term aspirin use do necessitate strategies for risk prevention, cautioned Dr Chan.

He said molecular and genetic markers in prostaglandin and inflammatory pathways hold particular promise for precision medicine. As part of a broader effort to tailor prevention strategies, Dr Chan and colleagues have led several studies into the mechanistic basis of aspirin’s anticancer effect, and, in turn, have developed intratumoral, colonic, germline, and circulating molecular correlates of outcomes.

“Such biomarkers can be exploited for risk stratification to more effectively target aspirin chemoprevention for those with more favorable risk-benefit profiles,” he said.

“Aspirin can impact multiple steps in the pathway, so you can imagine the potential. Even if patients develop resistance to 1 pathway, they can still be sensitive to aspirin because it can affect other pathways,” Dr Chan added.